Ординатура / Офтальмология / Английские материалы / Terminology and Guidelines for Glaucoma 3rd edition_European Glaucoma Society_2008

TREATMENT PRINCIPLES AND OPTIONS

3.3.1.2 - Category: ADRENERGIC ANTAGONISTS53,54

*ISA: Intrinsic Sympathomimetic Activity. The clinical relevance of ISA in glaucoma therapy has not yet been proven.

Action

Decreases intraocular pressure by reduction of the aqueous humor production. Peak effect in 2 hrs.

Dosage and administration [II,D]

Starting dose is one drop of lowest concentration of solution in the affected eye once or twice a day. If the clinical response is not adequate, the dosage may be increased to one drop of a higher concentration. Nyogel, Timolol in gelrite (Timoptic-XE, Timacar Depot, Timoptol XE, and Timosan) is given once daily.

No dose response curves for the different beta-blocker treatments have been established. The lowest concentration that would give the expected clinical effect should be used to avoid side defects. Dosing more than twice daily will not give any further pressure lowering effect.

Minimal extra effect with dipivefrine. No extra effect with adrenaline (epinephrine). Additive effect with most other IOP-lowering agents.

Preservativa-free preparations are available and may be considered.

Indications [II,D]

Elevation of intraocular pressure in patients where the IOP can be deleterious for the preservation of visual function.

Beta-1 selective adrenergic antagonist despite lowering IOP less than non selective, protect visual fi eld as well as non selective ones.

Major Contraindications [I,D]

Non-selective: Asthma, history of obstructive pulmonary disease, sinus bradycardia (< 60 beats/ min), heart block, or cardiac failure

Beta-1 selective:Relative contraindication in asthma, history of obstructive pulmonary disease, sinus bradycardia (< 60 beats/min), heart block, or cardiac failure

Most frequent side effects

Non-selective: Systemic: Bradycardia, arrhythmia, heart failure, syncope, bronchospasm, and airways obstruction.

Distal edema, hypotension. Depression. Hypoglycemia may be masked in insulin dependent diabetes

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TREATMENT PRINCIPLES AND OPTIONS

mellitus. Betablocking agents have been associated with nocturnal hypotension, which may be a risk factor in progression of glaucomatous optic nerve damage52.

Ocular (uncommon): Epithelial keratopathy, slight reduction in corneal sensitivity. Beta-1 selective: Better tolerated in most patients sensitive to non-selective agents.

Pregnancy and nursing mothers [I,D]

Only to be used if the potential benefi t justifi es the potential risk to the fetus or the infant.

Drug interactions

Oral or intravenous calcium antagonists: caution should be used in the co-administration of betaadrenergic blocking agents and oral or intravenous calcium antagonists, because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension [I,D].

Digitalis and calcium antagonists: the concomitant use of beta-adrenergic blocking agents with digitalis may have additive effects in prolonging conduction time.

Catecholamine-depleting drugs: possible additive effects and the production of hypotension and/or marked bradycardia.

Wash-out time

2-5 weeks.

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Mode of Action

Topical: Carbonic anhydrase inhibitor. Reduces aqueous formation resulting in lowered IOP. Systemic: Carbonic anhydrase inhibitor. Reduces aqueous formation resulting in lowered IOP.

Dosage and administration

Topical: Elevations of intraocular pressure in patients where the IOP can be deleterious for the preservation of visual function.

Systemic: When topical medications not effective or feasible. When long-term systemic CAI are needed, glaucoma surgery should be considered.

Major contraindications

Topical: Hypersensitivity to any component of the product

Systemic: Contraindicated in situations in which sodium and/or potassium blood levels are depressed, in cases of kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis.

Precautions

Topical: For the treatment of acute angle-closure glaucoma attack with corneal edema and infl amed conjunctiva, systemic CAI treatment is preferable.

In patients with low corneal endothelial cell count, there is increased risk of corneal edema.

Since no data on patients with severe renal impairment (CrCl < 30 mL/ml) are available, they should not be used in such patients. The concomitant use of topical and oral carbonic anhydrase inhibitors is not additive and not recommended.

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TREATMENT PRINCIPLES AND OPTIONS

These compounds are sulfonamides; the same kind of adverse reactions that are attributable to any sulphonamide may occur.

Systemic: Increasing the dose may increase the incidence of drowsiness and /or paresthesia. Adverse reaction common to all sulfonamide derivatives may occur ike anaphylaxis, fever rash (erythema multiforme), Stevens-Johnson syndrome, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Some of the above can be irreversible and lethal. If the patient is on another diuretic orally periodic monitoring of serum electrolytes is indicated.

Most frequent side effects

Topical: Ocular burning, stinging, bitter taste, superfi cial punctate keratitis, blurred vision, tearing, headache, urticaria, angioedema, pruritus, asthenia, dizziness, paresthesia and transient myopia.

Systemic: Paresthesias, hearing dysfunction, tinnitus, loss of appetite, taste

alteration gastrointestinal disturbances such as nausea, vomiting and diarrhoea. Depression, decreased libido, gastrointestinal symptoms, kidney stones, blood dyscrasias. Metabolic acidosis and electrolyte imbalance may occur.

Adverse reaction common to all sulfonamide derivatives may occur like anaphylaxis, fever rash (erythema multiforme), Steven-Johnson syndrome, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis.

Pregnancy and nursing mothers [I,D]

Topical: Only to be used if the potential benefi t justifi es the potential risk to the fetus or the infant.

Systemic: Only to be used if the potential benefi t justifi es the potential risk to the fetus or the infant. (Teratogenic effect seen from high doses of systemic CAIs in some animal species). Women of childbearing age should be warned of possible teratogenic effect.

Drug interactions

Topical: Specifi c drug interaction studies have not yet been performed.

Systemic: Should be used with caution in patients on steroid and systemic hypertension diuretic therapy because of the potential for developing hypokalemia [I,D].

Wash-out time

Topical CAI 1 week

Systemic CAI 3 days

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TREATMENT PRINCIPLES AND OPTIONS

3.3.1.4 - Category: PARASYMPATHOMIMETICS (CHOLINERGIC DRUGS)69,70

Mode of Action

Increase in facility of outfl ow of aqueous humor.

Direct action on longitudinal ciliary muscle.

Dosage and administration

Direct-acting:

Indirect-acting:

the morning.

Indications [II,D]

Direct-acting: Elevation of intraocular pressure in patients where the IOP can be deleterious for the preservation of

visual function.

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TREATMENT PRINCIPLES AND OPTIONS

Indirect-acting: POAG in aphakia / pseudophakia where surgery is refused or not feasible, in cases that are not controlled on other less potent agents.

These cases may respond satisfactory to ecothiophate iodide 0.03% or demecarium bromide 0.125% twice a day.

Major contraindications [I,D].

Direct-acting: Age < 40 yrs, cataract, uveitis and neovascular glaucoma. Assess possible worsening of pupillary block in each case of angle-closure glaucoma.

Indirect-acting: Active uveitis.

Precautions[I,D].

Direct-acting: Axial myopia, history of retinal detachment or rhegmatogenous retinal lesions. Indirect-acting: Should be used with extreme caution in patients with marked vagotonia,

bronchial asthma, spastic gastrointestinal disturbances, peptic ulcer, pronounced bradycardia and hypotension, recent myocardial infarction, epilepsy and Parkinsonism. Priory history of retinal detachment or rhegmatogenous retinal lesions.

General anesthesia with curarization.

Pregnancy and nursing mothers [I,D].

Direct-acting: Only to be used if the potential benefi t justifi es the potential risk to the fetus or the infant.

Indirect-acting: Contraindicated

Drug interactions [I,D]

Direct-acting: A competitive interaction on outfl ow with prostaglandins is assumed, since contraction of the ciliary muscle reduces the uveoscleral space.

Indirect-acting: Patients undergoing systemic anticholinesterase treatment should be warned of the possible additive effects of the indirect-acting parasympathomimetics. General anesthesia with muscle relaxants.

Wash-out time

Direct acting: 3 days

Indirect acting: several weeks. Some are irreversible.

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TREATMENT PRINCIPLES AND OPTIONS

3.3.1.5 - Category: PROSTAGLANDIN DERIVATIVES AND PROSTAMIDES61,72-91

*in alphabetic order

** approved in Denmark April 2008 and in Germany May 2008.

Mode of Action

For bimatoprost, latanoprost tafl uprost and travoprost the most evident action is the increase of the uveo-scleral outfl ow, reducing IOP 20% - 35%.

The IOP lowering effect of unoprostone is up to 18% from baseline. Unoprostone 0.12% has been available in Japan since 1994.

Pressure lowering effect:72-91

Reduction of the intraocular pressure starts approximately 2-4 hours after the fi rst administration with peak effect reached within approximately 8 to 12 hours. Maximum IOP lowering is often achieved 3 to 5 weeks from commencement of treatment

Dosage and administration

Bimatoprost 0.03%, latanoprost 0.005%, tafl uprost 0.0015% or travoprost 0.004% solution: once daily, preferably in the evening.

Unoprostone 0.12% and 0.15: b.i.d. (twice daily)

Indications [II,D]

Bimatoprost 0.03%, latanoprost 0.005%, and travoprost 0.004% solutions have received European (EMEA) and FDA approval as fi rst line drug for reducing intraocular pressure(IOP) in patients with open-angle glaucoma or ocular hypertension.

The prostaglandin analogues and prostamides appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. Most of the long-term data are published on latanoprost.

There are a few published clinical trials with bimatoprost, latanoprost, travoprost and unoprostone in treating angle-closure glaucoma, infl ammatory and neovascular glaucoma. Most of the large clinical trials of unoprostone are on the Japanese population. There are no comparative trials comparing these agents with laser trabeculoplasty.

This drug class offers potential as fi rst choice drugs or an alternative for patients who do not achieve control the target IOP with another topical antiglaucoma agent or for those with a contraindication to initial therapy with beta-adrenergic antagonists [II,D]. Based on meta-analysis of clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective and even more effective on IOP as timolol, 59 while the effectiveness of unoprostone is slightly less.

Prostaglandin analogues/prostamide may be used in conjunction with other antiglaucoma medications.

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TREATMENT PRINCIPLES AND OPTIONS

Fixed combinations of prostaglandin analogues/prostamide and timolol are now available in many European countries. Administered in the evening these fi xed combinations are at least as effective (non-inferior) as the components of the fi xed combinations given concurrently92-103.

Whether clinical experience will yield outcomes in favour of one of these products remains to be determined.

Patients should be educated on associated adverse events especially pigmentation of the iris and eyelashes [I,D].

Major contraindications [I,D]

Known hypersensitivity to bimatoprost / latanoprost / tafl uprost / travoprost / unoprostone, benzalkonium chloride, or any other product ingredient.

Patients should not administer these drugs while wearing contact lenses, but contact lenses can be reinserted 15 minutes following administration of the drugs.

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TREATMENT PRINCIPLES AND OPTIONS

Pregnancy and nursing mothers [I,D]

There are no adequate and well controlled studies in pregnant women. Only to be used during pregnancy if potential benefi t justifi es the potential risk to the fetus.

It is not known whether the drugs or their metabolites are excreted in human milk.

Drug interactions

Precipitation occurs when thiomerosal-containing eye drops are mixed with bimatoprost, latanoprost, or travoprost. Administer such drugs at least 5 minutes apart [I,D].

Wash-out time 4-6 weeks.

There is some ongoing discussion regarding differences between prostaglandin derivatives and prostamides, which has not been settled yet in the scientifi c community, but recently the prostamide receptor was described113,114. Some patients have been shown to respond differently to these agents. The EMEA has approved the use of the term prostamide.

3.3.1.6 - Osmotics

Hyperosmotics are the most effective agents to control acutely elevated IOP [I,D]. The patients must be evaluated for heart or kidney disease because hyperosmotics increase blood volume which increases the load on the heart [I,D]. They may alter glucose blood levels and should be given to diabetics only with great caution and monitoring [I,D].

-Glycerol 1.0 - 1.5 g/Kg orally

-Mannitol 1.0 - 1.5 g/Kg intravenously

3.3.2 - COMBINED DRUGS PREPARATIONS

Monotherapy fails to achieve a satisfactory IOP reduction in 40-75% of glaucoma patients after more than two years of therapy115,116. If monotherapy does not appear to lower the IOP satisfactory, replacement or switching monotherapy should be attempted before adding a second drug [II,D].(See FC IX) Multiple topical treatment should be avoided if possible as compliance is likely to suffer [I,D]. laser trabeculoplasty, if not done, should also be considered in open-angle glaucoma [II,D].

However, there are cases in which one drug is inadequate to lower a patient´s IOP to a desirable target pressure and add-on therapy is then required [I,D]. Use of β-blocker preparations with either a prostaglandin/prostamide, a carbonic anhydrase inhibitor, pilocarpine or with brimonidine have been shown to be more effective at IOP lowering than the use of one of these drugs separately118-129.

Rationale for adjunctive drug therapy

Antiglaucoma eye drops can be combined with each other, as well as added to laser and surgical treatments [I,D].

Drugs which belong to the same pharmacological group should not be used in combination (e.g. do not combine two different beta-blockers or two prostaglandin derivatives) [I,D].

-When available, fi xed-combined drugs preparations may be preferable than two separate instillations of the same agents; albeit not demonstrated so far, this might improve compliance by decreasing dosing schedule. [II,D] With fi xed combinations the eyes may be exposed to a reduced daily amount of preservative.

-In most patients is not recommended to use more than two drugs in two separate bottles or to add more than one single drug to a fi xed-combination. [II,D] (see Ch. 3.4).

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TREATMENT PRINCIPLES AND OPTIONS

-The additional drug(s) should be used only if needed to obtain the aimed-for target IOP.

-The effect of drug combinations is only measured in terms of IOP reduction.

-Assuming equal IOP effects, no drug combination is yet known to be preferable in terms of ONH or VF preservation.

-Increasing the recommended dosage will not result in increased IOP lowering and will only cause more side effects.

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